It is proposed to study the role of cyclic AMP and cyclic GMP in nervous tissue. One approach is to purify the two phosphoproteins obtained from synaptic membranes to prepare antibodies to these proteins, and to determine whether these antibodies affect synaptic transmission. A second approach is to evaluate the mechanism by which protein phosphorylation regulates the activity of tyrosine hydroxylase. A third approach is to study the functional significance of the phosphorylation of microtubular proteins. A fourth approach is to characterize a brain histamine-sensitive adenylate cyclase and to evaluate its possible significance as a component of the neurochemical events underlying synaptic transmission at histaminergic synapses. BIBLIOGRAPHIC REFERENCES: Krueger, B.K., Forn, J., and Greengard, P. (1975) Dopamine-sensitive adenylate cyclase and protein phosphorylation in the rat caudate nucleus. In Pre-and Post-Synaptic Receptors, pp. 123-147 of Volume 3 (E. Usdin and W.Bunney, Jr., volume editors) of Modern Pharmacology-Toxicology (W.F. Bousquet and R.F. Palmer, series editors) Marcel Dekker, New York. Ueda, T., Rudolph, S.A., and Greengard, P. (1975) solubilization of a phosphoprotein and its associated cyclic AMP-dependent protein kinase and phosphoprotein phosphatase from synaptic membrane fractions, and some kinetic evidence for their existence as a complex. Arch. Biochem. Biophys., 170, 492-503.